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ABSTRACT Iron is an indispensable micronutrient for all eukaryotic organisms due to its participation as a redox cofactor in many metabolic pathways. Iron imbalance leads to the most frequent human nutritional deficiency in the world. Adaptation to iron limitation requires a global reorganization of the cellular metabolism directed to prioritize iron utilization for essential processes. In response to iron scarcity, the conserved Saccharomyces cerevisiae mRNA-binding protein Cth2, which belongs to the tristetraprolin family of tandem zinc finger proteins, coordinates a global remodeling of the cellular metabolism by promoting the degradation of multiple mRNAs encoding highly iron-consuming proteins. In this work, we identify a critical mechanism for the degradation of Cth2 protein during the adaptation to iron deficiency. Phosphorylation of a patch of Cth2 serine residues within its amino-terminal region facilitates recognition by the SCFGrr1 ubiquitin ligase complex, accelerating Cth2 turnover by the proteasome. When Cth2 degradation is impaired by either mutagenesis of the Cth2 serine residues or deletion of GRR1, the levels of Cth2 rise and abrogate growth in iron-depleted conditions. Finally, we uncover that the casein kinase Hrr25 phosphorylates and promotes Cth2 destabilization. These results reveal a sophisticated posttranslational regulatory pathway necessary for the adaptation to iron depletion. IMPORTANCE Iron is a vital element for many metabolic pathways, including the synthesis of DNA and proteins, and the generation of energy via oxidative phosphorylation. Therefore, living organisms have developed tightly controlled mechanisms to properly distribute iron, since imbalances lead to nutritional deficiencies, multiple diseases, and vulnerability against pathogens. Saccharomyces cerevisiae Cth2 is a conserved mRNA-binding protein that coordinates a global reprogramming of iron metabolism in response to iron deficiency in order to optimize its utilization. Here we report that the phosphorylation of Cth2 at specific serine residues is essential to regulate the stability of the protein and adaptation to iron depletion. We identify the kinase and ubiquitination machinery implicated in this process to establish a posttranscriptional regulatory model. These results and recent findings for both mammals and plants reinforce the privileged position of E3 ubiquitin ligases and phosphorylation events in the regulation of eukaryotic iron homeostasis.

Background: Diabetic nephropathy (DN) is the most important complication of diabetes and the most common cause of end-stage renal disease (ESRD). Aims: A recent study established that the Ramulus mori polysaccharides (RMP) exert antioxidant effects on DN in rats. Methods: The diabetic rats which induced by high-fat diet and streptozotocin injection were orally administered RMP by doses of 250, 500 and 1000 mg/kg daily for 8 weeks. The effects of RMP on hyperglycemia and other biochemical changes were examined in the sera and kidney tissues. Additionally, the pathological and ultrastructural changes and expressions of nuclear-factor kappa B (NF-κB) and transforming growth factor-ß1 (TGF-ß1) were assessed. Results: The results revealed that the serum levels of blood glucose, total cholesterol (TC) and triglycerides (TG) were significantly decreased by RMP. Furthermore, the blood urea nitrogen (BUN), serum creatinine (SCr) and 24-hour urine protein levels in the RMP-medicated rats were lower than those in untreated diabetic rats. Moreover, treatment of the DN rats with RMP normalized all biochemical changes, including the malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels in the serum and kidney tissues. In contrast, the protein expression levels of NF-κB and TGF-ß1, which were enhanced in the kidneys of DN rats, were reduced by RMP. Conclusion: These results suggest that RMP improving the renal function of diabeitc rats possibly via its ameliorating antioxidant activities.

The root of Chuanminshen violaceum is used as an important edible and medicinal plant in China. However, its leaves are generally considered byproducts, and therefore do not have a use. Thus, the phenolic compounds in the methanolic extracts (CVLMs) and the chemical characteristics of crude polysaccharides (CVLPs) from the leaves of C. violaceum and their in vitro antioxidant activities were explored. The results showed that chlorogenic acid and rutin were the major individual phenolic compounds in the leaves, which ranged from 1.22 ± 0.03 to 2.87 ± 0.04 mg/g DW, and from 2.25 ± 0.04 to 4.03 ± 0.05 mg/g DW, respectively. Meanwhile, the extraction yields of CVLPs from the leaves ranged from 4.73% to 5.41%. The CVLPs consisted of mannose, rhamnose, galacturonic acid, glucose, galactose, and arabinose, suggesting the existence of pectic polysaccharides. Furthermore, both CVLMs and CVLPs exhibited strong antioxidant activities. Chlorogenic acid and rutin were major contributors to the antioxidant activities of CVLMs, and the antioxidant activities of CVLPs were closely correlated to their α-1,4-D-galactosiduronic linkages. The results are beneficial for understanding the chemical properties and in vitro antioxidant activities of CVLMs and CVLPs. The leaves of C. violaceum have potential to be developed as natural antioxidants.

This is the first study on the effect of carbonic maceration on the quality (color, aroma profile and sensory properties) of Muscat Hamburg, contrasting two winemaking procedures used in Tianjin (classical white and red-winemaking techniques). The values of C* (psychometric chroma), a* (measure of redness) and b* (measure of yellowness) were significantly higher (p < 0.01) in the carbonic macerated wine than in red wine. However, there were no visual differences in color, and classical red wine and carbonic macerated wine had similar h (hue angle) values and located in the red region. Thirty-two aromatic compounds were identified and quantified in Muscat Hamburg wines. The content of volatile compounds (6384.97 μg/L) was significantly higher (p < 0.001) in the carbonic macerated Muscat Hamburg wine than in the other kinds of wine. This result led to the carbonic macerated wine having the highest odor activity values (OAVs) and sensory evaluation scores (86.8 points), which correlates with an “excellent” sensory perception. This study demonstrated that carbonic maceration significantly improved the quality of Muscat Hamburg wine based on volatile analysis and sensory evaluation compared with other conventional methods. Therefore, carbonic maceration could be well suited for making Muscat Hamburg wine.

Oxidative stress leads to various diseases, including diabetes, cardiovascular diseases, neurodegenerative diseases, and even cancer. The dietary flavonol glycoside, hyperoside (quercetin-3-O-galactoside), exerts health benefits by preventing oxidative damage. To further understand its antioxidative defence mechanisms, we systemically investigated the regulation of hyperoside on oxidative damage induced by hydrogen peroxide, carbon tetrachloride, and cadmium in Saccharomyces cerevisiae. Hyperoside significantly increased cell viability, decreased lipid peroxidation, and lowered intracellular reactive oxygen species (ROS) levels in the wild-type strain (WT) and mutants gtt1∆ and gtt2∆. However, the strain with ctt1∆ showed variable cell viability and intracellular ROS-scavenging ability in response to the hyperoside treatment upon the stimulation of H2O2 and CCl4. In addition, hyperoside did not confer viability tolerance or intercellular ROS in CdSO4-induced stress to strains of sod1∆ and gsh1∆. The results suggest that the antioxidative reactions of hyperoside in S. cerevisiae depend on the intercellular ROS detoxification system.

Ultra-tight integration was first proposed by Abbott in 2003 with the purpose of integrating a global navigation satellite system (GNSS) and an inertial navigation system (INS). This technology can improve the tracking performances of a receiver by reconfiguring the tracking loops in GNSS-challenged environments. In this paper, the models of all error sources known to date in the phase lock loops (PLLs) of a standard receiver and an ultra-tightly integrated GNSS/INS receiver are built, respectively. Based on these models, the tracking performances of the two receivers are compared to verify the improvement due to the ultra-tight integration. Meanwhile, the PLL error distributions of the two receivers are also depicted to analyze the error changes of the tracking loops. These results show that the tracking error is significantly reduced in the ultra-tightly integrated GNSS/INS receiver since the receiver’s dynamics are estimated and compensated by an INS. Moreover, the mathematical relationship between the tracking performances of the ultra-tightly integrated GNSS/INS receiver and the quality of the selected inertial measurement unit (IMU) is derived from the error models and proved by the error comparisons of four ultra-tightly integrated GNSS/INS receivers aided by different grade IMUs.

This work focuses on the effect of remote phonon arising from the substrate and high-κ gate dielectric on electron mobility in two-dimensional (2D) InSe field-effect transistors (FETs). The electrostatic characteristic under quantum confinement is derived by self-consistently solving the Poisson and Schrödinger equations using the effective mass approximation. Then mobility is calculated by the Kubo⁻Greenwood formula accounting for the remote phonon scattering (RPS) as well as the intrinsic phonon scatterings, including the acoustic phonon, homopolar phonon, optical phonon scatterings, and Fröhlich interaction. Using the above method, the mobility degradation due to remote phonon is comprehensively explored in single- and dual-gate InSe FETs utilizing SiO2, Al2O3, and HfO2 as gate dielectric respectively. We unveil the origin of temperature, inversion density, and thickness dependence of carrier mobility. Simulations indicate that remote phonon and Fröhlich interaction plays a comparatively major role in determining the electron transport in InSe. Mobility is more severely degraded by remote phonon of HfO2 dielectric than Al2O3 and SiO2 dielectric, which can be effectively insulated by introducing a SiO2 interfacial layer between the high-κ dielectric and InSe. Due to its smaller in-plane and quantization effective masses, mobility begins to increase at higher density as carriers become degenerate, and mobility degradation with a reduced layer number is much stronger in InSe compared with MoS2.

A bidirectional threshold switching (TS) characteristic was demonstrated in Ag/ZrO2/Pt electrochemical metallization cells by using the electrochemical active Ag electrode and appropriate programming operation strategies The volatile TS was stable and reproducible and the rectify ratio could be tuned to ∼107 by engineering the compliance current. We infer that the volatile behavior is essentially due to the moisture absorption in the electron beam evaporated films, which remarkably improved the anodic oxidation as well as the migration of Ag+ ions. The resultant electromotive force would act as a driving force for the metal filaments dissolution, leading to the spontaneous volatile characteristics. Moreover, conductance quantization behaviors were also achieved owing to formation and annihilation of atomic scale metal filaments in the film matrix. Our results illustrate that the Ag/ZrO2/Pt device with superior TS performances is a promising candidate for selector applications in passive crossbar arrays.

Trachoma, a contagious keratoconjunctivitis(KC), caused by Chlamydia trachomatis infection, is rife in 57 countries in the world at present. The World Health Organization(WHO)listed the global alliance to eliminate blinding trachoma by 2020 as one of top priorities of its blindness prevention in 1998. A simplified classification system for identifying and naming trachoma, designated by WHO, and the SAFE strategy based on community intervention were extended continuously in the world in 10 years since then. The trachoma prevalence trend has showed a change compared with that in the past. China has launched the blindness prevention action, aimed to eliminate blinding trachoma by 2016. In this paper,we reviews progress in diagnosis, treatment and epidemic of trachoma since the extension of the SAFE strategy.

The electrical performance of MoS2 can be engineered by introducing high-κ dielectrics, while the interactions between high-κ dielectrics and MoS2 need to be studied. In this study, multilayer MoS2 field-effect transistors (FETs) with a back-gated configuration were fabricated on high-κ Al2O3 coated Si substrates. Compared with MoS2 FETs on SiO2, the field-effect mobility (μFE) and subthreshold swing (SS) were remarkably improved in MoS2/Al2O3/Si. The improved μFE was thought to result from the dielectric screening effect from high-κ Al2O3. When a HfO2 passivation layer was introduced on the top of MoS2/Al2O3/Si, the field-effect mobility was further enhanced, which was thought to be concerned with the decreased contact resistance between the metal and MoS2. Meanwhile, the interface trap density increased from 2.4×1012 eV−1cm−2 to 6.3×1012 eV−1cm−2. The increase of the off-state current and the negative shift of the threshold voltage may be related to the increase of interface traps.

Background. Rapid atrial pacing (RAP) can induce electrical and autonomic remodeling and facilitate atrial fibrillation (AF). Recent reports showed that low-level vagosympathetic nerve stimulation (LLVNS) can suppress AF, as an antiarrhythmic effect. We hypothesized that LLVNS can reverse substrate heterogeneity induced by RAP. Methods and Results. Mongrel dogs were divided into (LLVNS+RAP) and RAP groups. Electrode catheters were sutured to multiple atrial sites, and LLVNS was applied to cervical vagosympathetic trunks with voltage 50% below the threshold slowing sinus rate by ⩽30 msec. RAP induced a significant decrease in effective refractory period (ERP) and increase in the window of vulnerability at all sites, characterized by descending and elevated gradient differences towards the ganglionic plexi (GP) sites, respectively. The ERP dispersion was obviously enlarged by RAP and more significant when the ERP of GP-related sites was considered. Recovery time from AF was also prolonged significantly as a result of RAP. LLVNS could reverse all these changes induced by RAP and recover the heterogeneous substrate to baseline. Conclusions. LLVNS can reverse the electrical and autonomic remodeling and abolish the GP-central gradient differences induced by RAP, and thus it can recover the homogeneous substrate, which may be the underlying mechanism of its antiarrhythmic effect.

In the crystal structure of the title compound, C5H8N2O, molecules are linked by weak C—H...O hydrogen bonds, forming a three-dimensional network.

AIM: To make a survey on people suffering trachoma in Gansu province, and to provide evidence for developing trachoma control and prevention therapy.METHODS: We chose the zone on the basis of relative information. Provincial Office of Blindness Prevention carried out the survey in 3 counties including Tange Township of Wushan, Xiqu Township of Minqin and Hulinjia Township of Jishishan from October 14, 2013 to November 23, 2013. One hundred and fifty primary school students were selected, including 72 boys and 78 girls aging from 5a to 10a with the average age of 7.5y. The targeted students received the fast trachoma assessment by the adoption of simplified trachoma classification system which was recommended by the World Health Organization. RESULTS: No case of active trachoma, trachomatous trichiasis and corneal disease were examined among 150 students. CONCLUSION: The rate of trachoma is low in Gansu province. But we still cannot get the conclusion that there is no epidemic of trachoma in Gansu. And we need to further expand the survey scope to correctly assess the trachoma case and to provide reliable evidence for trachoma prevention and control.

Dyslipidemia is the most prevalent independent risk factor for patients with chronic kidney disease (CKD). Lipid-induced NLRP3 inflammasome activation in kidneyresident cells exacerbates renal injury by causing sterile inflammation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that modulates the cellular redox balance; however, the exact role of Nrf2 signaling and its regulation of the NLRP3 inflammasome in hyperlipidemia-induced kidney injury are poorly understood. In this study, we demonstrated that activation of the mtROS--NLRP3 inflammasome pathway is a critical contributor to renal tubular epithelial cell (RTEC) apoptosis under hyperlipidemia. In addition, the Nrf2/ARE signaling pathway is activated in renal tubular epithelial cells under hyperlipidemia conditions both in vivo and in vitro, and Nrf2 silencing accelerated palmitic acid (PA)-induced mtROS production, mitochondrial injury, and NLRP3 inflammasome activation. However, the activation of Nrf2 with tBHQ ameliorated mtROS production, mitochondrial injury, NLRP3 inflammasome activation, and cell apoptosis in PA-induced HK-2 cells and in the kidneys of HFD-induced obese rats. Furthermore, mechanistic studies showed that the potential mechanism of Nrf2-induced NLRP3 inflammasome inhibition involved reducing mtROS generation. Taken together, our results demonstrate that the Nrf2/ARE signaling pathway attenuates hyperlipidemiainduced renal injury through its antioxidative and anti-inflammatory effects through the downregulation of mtROS-mediated NLRP3 inflammasome activation. [ABSTRACT FROM AUTHOR]